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https://www.readbyqxmd.com/read/28404526/stereospecific-cholinesterase-inhibition-by-o-s-diethylphenylphosphonothioate
#1
Ahmed Mohammed, Jennifer Sneathen, Sara Glazier Frojen, Louis Kuo, Cynthia M Dupureur
The inhibition kinetics and stereospecificity of the chiral nerve agent derivative O,S-diethylphenylphosphonothioate (DEPP) were examined for two forms of acetylcholinesterase (human and eel) and equine butyrylcholinesterase. Both S- and R-DEPP are poor inhibitors of eel AChE (IC50 150μM), consistent with a large, nondiscriminatory binding interaction in the active site of this enzyme. However, S-DEPP is active against human and equine AChE with low μM IC50s. DEPP stereospecificities (S/R) toward these enzymes are moderate (20) relative to other cholinesterase-organophosphate (OP) systems...
March 30, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28403672/toxic-megacolon-as-a-rare-complication-following-atropine-therapy-due-to-organophosphate-poisoning-a-case-report
#2
Babak Mostafazadeh, Esmaeil Farzaneh, Maryam Paeezi, Farahnaz Nikkhah
The main therapeutic basis for a case of organophosphate poisoning is a combination therapy which includes atropine as an anticholinergic drug and pralidoxime. If the poisoning is severe, a high dose of this combination of medicines may be needed, but this may cause serious side effects: paralytic ileus or even megacolon; however, these gastrointestinal events are very rare. Here, we report a case of organophosphate poisoning where atropine therapy was given and led to drug-associated toxic megacolon.
January 1, 2017: Medico-legal Journal
https://www.readbyqxmd.com/read/28329845/spatiotemporal-progression-and-remission-of-lesions-in-the-rat-brain-following-acute-intoxication-with-diisopropylfluorophosphate
#3
Sílvia Sisó, Brad A Hobson, Danielle J Harvey, Donald A Bruun, Douglas J Rowland, Joel R Garbow, Pamela J Lein
Similar to organophosphate (OP) nerve agents, diisopropylfluorophosphate (DFP) rapidly and irreversibly inhibits acetylcholinesterase, leading to convulsions that can progress to status epilepticus (SE). However, in contrast to the OP nerve agents, the long-term consequences of DFP-induced SE are not well known. Thus, we characterized the spatiotemporal profile of neuropathology during the first two months following acute DFP intoxication. Adult, male Sprague Dawley rats administered pyridostigmine bromide (0...
March 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28329842/magnetic-resonance-imaging-reveals-progressive-brain-injury-in-rats-acutely-intoxicated-with-diisopropylfluorophosphate
#4
Brad A Hobson, Sílvia Sisó, Douglas J Rowland, Danielle J Harvey, Donald A Bruun, Joel R Garbow, Pamela J Lein
Acute intoxication with organophosphates (OPs) can trigger seizures that progress to status epilepticus, and survivors often exhibit chronic neuropathology, cognitive impairment, affective disorders and/or electroencephalographic abnormalities. Understanding how acute injury transitions to persistent neurological sequelae is critical to developing medical countermeasures for mitigating damage following OP-induced seizures. Here, we used in vivo magnetic resonance imaging (MRI) to monitor the spatiotemporal patterns of neuropathology for one month after acute intoxication with diisopropylfluorophosphate (DFP)...
March 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28328690/the-first-use-of-pralidoxime-in-a-child-with-rivastigmine-poisoning
#5
Eylem Ulaş Saz, Ali Yurtseven, Mehmet Arda Kilinç, Yusuf Sari, Hasan Ağin
The aim of this report is to describe the successful use of pralidoxime in a pediatric patient who accidentally ingested 12 mg of rivastigmine and presented to the emergency department with weakness, drowsiness, hyporeactivity to environmental stimuli, and full cholinergic syndrome. CASE: The patient presented to the emergency department 2 hours after a suspected ingestion of rivastigmine. He was sleepy but oriented and cooperative, hypotonic, and hyporeflexic and has a Glasgow Coma Scale score of 13 (E3M6V4)...
March 21, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28296779/efficacy-of-fresh-packed-red-blood-transfusion-in-organophosphate-poisoning
#6
RANDOMIZED CONTROLLED TRIAL
Hang-Xing Bao, Pei-Jian Tong, Cai-Xia Li, Jing Du, Bing-Yu Chen, Zhi-Hui Huang, Ying Wang
The mortality rate caused by organophosphate (OP) poisoning is still high, even the standard treatment such as atropine and oxime improves a lot. To search for alternative therapies, this study was aimed to investigate the effects of packed red blood cell (RBC) transfusion in acute OP poisoning, and compare the therapeutic effects of RBCs at different storage times.Patients diagnosed with OP poisoning were included in this prospective study. Fresh RBCs (packed RBCs stored less than 10 days) and longer-storage RBCs (stored more than 10 days but less than 35 days) were randomly transfused or not into OP poisoning patients...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28106328/on-the-influence-of-the-protonation-states-of-active-site-residues-on-ache-reactivation-a-qm-mm-approach
#7
Thomas Driant, Florian Nachon, Cyril Ollivier, Pierre-Yves Renard, Etienne Derat
Acetylcholinesterase (AChE), an enzyme of the serine hydrolase superfamily, is a mediator of signal transmission at cholinergic synapses by catalyzing acetylcholine cleavage into acetate and choline. This enzyme is vulnerable to covalent inhibition by organophosphate compounds (like VX). Covalent inhibition of AChE does not revert spontaneously. Known reactivator compounds have limited action in restoring catalytic activity. QM/MM simulations of VX-inhibited AChE reactivation by pralidoxime (2-PAM), a classical reactivator, were performed...
January 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28078916/in-vivo-protection-studies-of-bis-quaternary-2-hydroxyimino-n-pyridin-3-yl-acetamide-derivatives-hnk-oximes-against-tabun-and-soman-poisoning-in-swiss-albino-mice
#8
P Kumar, D Swami, D P Nagar, K P Singh, J Acharya, H N Karade, R Yadav
The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28043418/the-effectiveness-of-patient-tailored-treatment-for-acute-organophosphate-poisoning
#9
RANDOMIZED CONTROLLED TRIAL
Chih-Chuan Lin, Dong-Zong Hung, Hsien-Yi Chen, Kuang-Hung Hsu
BACKGROUND: To determine a new pralidoxime (PAM) treatment guideline based on the severity of acute organophosphate intoxication patients, APACHE II score, and dynamic changes in serum butyrylcholinesterase (BuChE) activity. METHODS: This is a randomization trial. All patients received supportive care measurements and atropinization. Each enrolled patient was treated with 2 gm PAM intravenously as the loading dose. The control group was treated according to the WHO's recommended PAM regimen, and the experimental group was treated according to their APACHE II scores and dynamic changes in BuChE activity...
December 2016: Biomedical Journal
https://www.readbyqxmd.com/read/28043415/pralidoxime-and-pesticide-poisoning-a-question-of-severity
#10
EDITORIAL
Emma Louise Walton
In this issue of the Biomedical Journal, we highlight new data supporting the use of pralidoxime in the treatment of cases of organophosphate poisoning, which also suggest that WHO treatment guidelines should be updated. We also learn about a modified surgical technique to repair severe spinal injuries, as well as new insight into the structure of human adenovirus that could inform vaccine development.
December 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27990564/planarian-cholinesterase-in-vitro-characterization-of-an-evolutionarily-ancient-enzyme-to-study-organophosphorus-pesticide-toxicity-and-reactivation
#11
Danielle Hagstrom, Hideto Hirokawa, Limin Zhang, Zoran Radic, Palmer Taylor, Eva-Maria S Collins
The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D...
December 18, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27728587/pralidoxime-in-acute-organophosphate-poisoning-a-randomized-trial
#12
Bammigatti C, M Vinod Babu, T Kadhiravan, R P Swaminathan
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27651556/acute-poisoning-in-a-child-following-topical-treatment-of-head-lice-pediculosis-capitis-with-an-organophosphate-pesticide
#13
Muddathir H Hamad, Ahmed Awad Adeel, Ali Abdu N Alhaboob, Ahmed M Ashri, Mustafa A Salih
This is a case report of acute organophosphate poisoning in a child treated with topical application of Diazinon-60 (WHO Class II toxicity) for head lice (pediculosis capitis). The patient presented with neurological symptoms and signs. After emergency respiratory and circulatory resuscitation the patient underwent dermal decontamination and was treated with atropine, high flow oxygen and pralidoxime. Scanning electron micrographs of scalp hair specimens revealed both viable and empty head lice nits (lice eggs that attach to the hair shaft)...
2016: Sudanese Journal of Paediatrics
https://www.readbyqxmd.com/read/27432237/toxicity-and-median-effective-doses-of-oxime-therapies-against-percutaneous-organophosphorus-pesticide-and-nerve-agent-challenges-in-the-hartley-guinea-pig
#14
COMPARATIVE STUDY
Thomas H Snider, Michael C Babin, David A Jett, Gennady E Platoff, David T Yeung
Anticholinesterases, such as organophosphorus pesticides and warfare nerve agents, present a significant health threat. Onset of symptoms after exposure can be rapid, requiring quick-acting, efficacious therapy to mitigate the effects. The goal of the current study was to identify the safest antidote with the highest therapeutic index (TI = oxime 24-hr LD50/oxime ED50) from a panel of four oximes deemed most efficacious in a previous study. The oximes tested were pralidoxime chloride (2-PAM Cl), MMB4 DMS, HLö-7 DMS, and obidoxime Cl2...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27418928/the-effect-of-parathion-on-red-blood-cell-acetylcholinesterase-in-the-wistar-rat
#15
Naofumi Bunya, Keigo Sawamoto, Hanif Benoit, Steven B Bird
Organophosphorus (OP) pesticide poisoning is a significant problem worldwide. Research into new antidotes for these acetylcholinesterase inhibitors, and even optimal doses for current therapies, is hindered by a lack of standardized animal models. In this study, we sought to characterize the effects of the OP pesticide parathion on acetylcholinesterase in a Wistar rat model that included comprehensive medical care. Methods. Male Wistar rats were intubated and mechanically ventilated and then poisoned with between 20 mg/kg and 60 mg/kg of intravenous parathion...
2016: Journal of Toxicology
https://www.readbyqxmd.com/read/27396356/in-vitro-characterization-of-pralidoxime-transport-and-acetylcholinesterase-reactivation-across-mdck-cells-and-stem-cell-derived-human-brain-microvascular-endothelial-cells-bc1-hbmecs
#16
Erin Gallagher, Il Minn, Janice E Chambers, Peter C Searson
BACKGROUND: Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. METHODS: To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs)...
July 11, 2016: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/27266642/-acute-poisoning-by-pesticides-in-children
#17
REVIEW
P Leveau
Acute pesticide poisoning in children is rare but potentially serious. Some clinical patterns (toxidromes) are suggestive of the drug class: cholinergic crisis for organophosphate or carbamate insecticides; neurological syndrome for rodenticides; digestive and respiratory syndrome for herbicides. Treatment is symptomatic and only a few patients are treated with an antidote: atropine and pralidoxime for organophosphate insecticides, vitamin K for anticoagulant rodenticides.
July 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/27179675/a-liquid-chromatography-tandem-mass-spectrometric-method-on-in-vitro-nerve-agents-poisoning-characterization-and-reactivator-efficacy-evaluation-by-determination-of-specific-peptide-adducts-in-acetylcholinesterase
#18
Long Yan, Jia Chen, Bin Xu, Lei Guo, Yan Xie, Jijun Tang, Jianwei Xie
The terroristic availability of highly toxic nerve agents (NAs) highlights the necessity for a deep understanding of their toxicities and effective medical treatments. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for a characterization of the NAs poisoning and an evaluation on the efficacy of reactivators in in vitro was developed for the first time. After exposure to sarin or VX and pepsin digestion, the specific peptides of acetylcholinesterase (AChE) in a purified status, i.e. undecapeptide "GESAGAASVGM" in free, unaged, or aged status was identified and quantified...
June 10, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27158860/intramuscular-versus-intraosseous-delivery-of-nerve-agent-antidote-pralidoxime-chloride-in-swine
#19
Nabeel I Uwaydah, Stephen L Hoskins, Stephen P Bruttig, Henry Farrar, Nick C Copper, Donald J Deyo, Michael A Dubick, George C Kramer
OBJECTIVE: Exposure to nerve agents requires prompt treatment. We hypothesized that intraosseous (IO) injections of drug antidotes into the vascularized bone marrow will provide a more rapid and effective means to treat exposure to nerve agents than standard intramuscular (IM) injections. We compared the pharmacokinetics of IM and IO administration of pralidoxime chloride (2-PAM Cl) during normovolemia and hypovolemia, as well as their combined administration during normovolemia in swine...
July 2016: Prehospital Emergency Care
https://www.readbyqxmd.com/read/27125761/oximes-in-organophosphate-poisoning-60-years-of-hope-and-despair
#20
Franz Worek, Horst Thiermann, Timo Wille
The high number of annual fatalities following suicidal poisoning by organophosphorus (OP) pesticides and the recent homicidal use of the chemical warfare nerve agent sarin against civilian population in Syria underlines the continuous threat by these highly toxic agents. The need for an effective treatment of OP poisoning resulted in the implementation of a combination therapy with the muscarinic receptor antagonist atropine and an oxime for the reactivation of OP-inhibited acetylcholinesterase (AChE). Since the invention of the first clinically used oxime pralidoxime (2-PAM) in the 1950s ongoing research attempted to identify more effective oximes...
November 25, 2016: Chemico-biological Interactions
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